Managing the risk of transfusion-transmitted malaria from Australian blood donations: Recommendation of a new screening strategy.

BACKGROUND AND OBJECTIVES: To reduce the risk of transfusion-transmitted malaria (TTM) from transfusible components, Australia tests for malaria antibodies in both travellers returning from and former residents of malaria-endemic areas. The testing is performed a minimum of 120 days after last potential exposure. TTM is an extremely rare event and managing the risk adds considerable complexity. The objectives of this study were to analyse various testing and deferral strategies, considering the risk, donation numbers and operational complexities. MATERIALS AND METHODS: A residual risk model was developed to calculate the risk of TTM in five testing/deferral strategies. Australian blood donor data from 2020 and 2021 were used and incorporated the incidence of parasitaemia, Plasmodium species and the malaria enzyme immunoassay test's failure rate. Donor and donation loss or gain and an operational assessment were performed. RESULTS: The current model's estimated risk of TTM is 1 in 67.9 million transfused units. Testing residents with a 120-day plasma restriction for visitors without testing was found to have the same estimated risk, with an expected increase of 342 donations per year, significant cost savings and a 62% reduction in the number of donors requiring assessment. CONCLUSION: A strategy that involves testing residents of malaria areas only and a 120-day plasma travel restriction would not significantly increase the risk of TTM, is operationally simpler, costs less and results in a small increase in donations.

Optimal malarial screening strategy in Australian blood donors: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted malaria (TTM) infections is extremely low in Australia, and the cost-effectiveness of the current screening strategy has not been assessed. This study aims to conduct a cost-effectiveness analysis of different malaria screening strategies in blood donors as part of the risk-based decision-making framework. MATERIALS AND METHODS: A decision tree model was developed to assess the cost-effectiveness of five alternative malaria screening strategies from a healthcare sector perspective. Screening strategies combining total or partial removal of malaria testing with different deferral periods were considered. The probabilities of developing severe and uncomplicated TTM were based on a literature review of cases in non-endemic areas since 2000. The health outcomes were quantified using disability-adjusted life years. The costs of non-returning donors due to deferral were also included. Deterministic and probabilistic sensitivity analyses were conducted to account for data uncertainty. RESULTS: The residual risks for all strategies were so low that the costs, mortality and morbidity associated with TTM are almost negligible. The overall costs were predominantly influenced by the costs of non-returning blood donors. As a result, removal of malaria testing and applying a 28-day deferral for at-risk donors were the least costly and most cost-effective of all the options considered. CONCLUSION: The current screening strategy for malaria in blood donors in Australia is not an efficient use of healthcare resources. Partial or total removal of malaria testing would bring significant cost savings without significantly compromising blood safety.

Removing hepatitis C antibody testing for Australian blood donations: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted hepatitis C virus (HCV) infections is extremely low in Australia. This study aims to conduct a cost-effectiveness analysis of different testing strategies for HCV infection in blood donations. MATERIALS AND METHODS: The four testing strategies evaluated in this study were universal testing with both HCV antibody (anti-HCV) and nucleic acid testing (NAT); anti-HCV and NAT for first-time donations and NAT only for repeat donations; anti-HCV and NAT for transfusible component donations and NAT only for plasma for further manufacture; and universal testing with NAT only. A decision-analytical model was developed to assess the cost-effectiveness of alternative HCV testing strategies. Sensitivity analysis and threshold analysis were conducted to account for data uncertainty. RESULTS: The number of potential transfusion-transmitted cases of acute hepatitis C and chronic hepatitis C was approximately zero in all four strategies. Universal testing with NAT only was the most cost-effective strategy due to the lowest testing cost. The threshold analysis showed that for the current practice to be cost-effective, the residual risks of other testing strategies would have to be at least 1 HCV infection in 2424 donations, which is over 60,000 times the baseline residual risk (1 in 151 million donations). CONCLUSION: The screening strategy for HCV in blood donations currently implemented in Australia is not cost-effective compared with targeted testing or universal testing with NAT only. Partial or total removal of anti-HCV testing would bring significant cost savings without compromising blood recipient safety.

Is dual testing for hepatitis C necessary? Modelling the risk of removing hepatitis C antibody testing for Australian blood donations.

BACKGROUND AND OBJECTIVES: Parallel testing of blood donations for hepatitis C virus (HCV) antibody and HCV RNA by nucleic acid testing (NAT) has been standard practice in Australia since 2000. Meanwhile, NAT technologies have improved, and HCV has become a curable disease. This has resulted in a significant reduction in the risk and clinical consequences of HCV transmission through transfusion. This study aimed to estimate the residual risk (RR) under various testing options to determine the optimal testing strategy. MATERIALS AND METHODS: A developed deterministic model calculated the RR of HCV transmission for four testing strategies. A low, mid and high estimate of the RR was calculated for each. The testing strategies modelled were as follows: universal dual testing, targeted dual testing for higher risk groups (first-time donors or transfusible component donations) and universal NAT only. RESULTS: The mid estimate of the RR was 1 in 151 million for universal dual testing, 1 in 111 million for targeted dual testing of first-time donors, 1 in 151 million for targeted dual testing for transfusible component donations and 1 in 66 million for universal NAT only. For all testing strategies, all estimates were considerably less than 1 in 1 million. CONCLUSION: Antibody testing in addition to NAT does not materially change the risk profile. Even conservative estimates for the cessation of anti-HCV predict an HCV transmission risk substantially below 1 in 1 million. Therefore, given that it is not contributing to blood safety in Australia but consuming resources, anti-HCV testing can safely be discontinued.

Opinion amplification causes extreme polarization in social networks.

Extreme polarization of opinions fuels many of the problems facing our societies today, from issues on human rights to the environment. Social media provides the vehicle for these opinions and enables the spread of ideas faster than ever before. Previous computational models have suggested that significant external events can induce extreme polarization. We introduce the Social Opinion Amplification Model (SOAM) to investigate an alternative hypothesis: that opinion amplification can result in extreme polarization. SOAM models effects such as sensationalism, hype, or "fake news" as people express amplified versions of their actual opinions, motivated by the desire to gain a greater following. We show for the first time that this simple idea results in extreme polarization, especially when the degree of amplification is small. We further show that such extreme polarization can be prevented by two methods: preventing individuals from amplifying more than five times, or through consistent dissemination of balanced opinions to the population. It is natural to try and have the loudest voice in a crowd when we seek attention; this work suggests that instead of shouting to be heard and generating an uproar, it is better for all if we speak with moderation.

From evolutionary ecosystem simulations to computational models of human behavior.

We have a wide breadth of computational tools available today that enable a more ethical approach to the study of human cognition and behavior. We argue that the use of computer models to study evolving ecosystems provides a rich source of inspiration, as they enable the study of complex systems that change over time. Often employing a combination of genetic algorithms and agent-based models, these methods span theoretical approaches from games to complexification, nature-inspired methods from studies of self-replication to the evolution of eyes, and evolutionary ecosystems of humans, from entire economies to the effects of personalities in teamwork. The review of works provided here illustrates the power of evolutionary ecosystem simulations and how they enable new insights for researchers. They also demonstrate a novel methodology of hypothesis exploration: building a computational model that encapsulates a hypothesis of human cognition enables it to be tested under different conditions, with its predictions compared to real data to enable corroboration. Such computational models of human behavior provide us with virtual test labs in which unlimited experiments can be performed. This article is categorized under: Computer Science and Robotics > Artificial Intelligence.

The Surprising Creativity of Digital Evolution: A Collection of Anecdotes from the Evolutionary Computation and Artificial Life Research Communities.

Evolution provides a creative fount of complex and subtle adaptations that often surprise the scientists who discover them. However, the creativity of evolution is not limited to the natural world: Artificial organisms evolving in computational environments have also elicited surprise and wonder from the researchers studying them. The process of evolution is an algorithmic process that transcends the substrate in which it occurs. Indeed, many researchers in the field of digital evolution can provide examples of how their evolving algorithms and organisms have creatively subverted their expectations or intentions, exposed unrecognized bugs in their code, produced unexpectedly adaptations, or engaged in behaviors and outcomes, uncannily convergent with ones found in nature. Such stories routinely reveal surprise and creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. Bugs are fixed, experiments are refocused, and one-off surprises are collapsed into a single data point. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This article is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems.

Ensuring donor safety: is venesecting therapeutic donors to haemoglobin levels below Blood Service guidelines safe?

Therapeutic phlebotomy is the cornerstone of treatment for HFE haemochromatosis (HH). Current Australian Red Cross LifeBlood Service guidelines mandate measuring haemoglobin (Hb) levels prior to phlebotomy and if below 130 g/l in men or 120 g/l in women, donors are deferred from donating whole blood. Therapeutic donation below these levels may take place where both the treating doctor and a blood service medical officer approve. The aim of the current study was to determine whether adverse events are more frequent in those who undergo therapeutic phlebotomy below current Hb thresholds applied to volunteer therapeutic donors. A retrospective review of all therapeutic donations was undertaken for the financial year 2016-2017. The data were obtained through the Australian Red Cross Blood Service. Inclusion criteria were any donor between 16 and 70 years of age, weighing more than 50 kg and meeting blood service guidelines for donation. All adverse events recorded in an electronic quality system were obtained and associated with donor haemoglobin level. Statistical analyses were performed using analysis of variance or Fisher's exact test (GraphPad Prism). About 34 886 therapeutic phlebotomy donations occurred during 2016-2017, of whom the majority were referred for HH (34 089). In total, 365 of 34 886 donations (0·0105%) were complicated by an adverse event. A total of 305 (0·0087%) therapeutic donations occurred while below the lower limit of blood service Hb threshold for their respective genders. Of the donations that occurred below the blood service threshold, 3 of 305 (0·0098%) had an adverse event compared with 362 of 34 581 donations above the lower limit threshold (0·0105%, P = 0·99). The incidence of adverse events was not increased in the group which underwent therapeutic phlebotomy below the current Australian Red Cross Blood Service Hb threshold compared with those above threshold, indicating safety of treatment at Hb levels lower than currently recommended.

Modelling the risk of transfusion-transmitted syphilis: a reconsideration of blood donation testing strategies.

BACKGROUND AND OBJECTIVES: Donor syphilis testing began in the 1940s amidst widespread transfusion-transmitted syphilis (TTS). Since then, the introduction of penicillin, pre-donation screening questionnaires and improved storage conditions have contributed to reducing transmission risk. Consequently, universal testing may no longer be cost-effective. This study analysed alternative options for donor syphilis testing to determine the optimal strategy. MATERIALS AND METHODS: A model was developed using conservative parameter estimates for factors affecting TTS and 2009-2015 Australian donations to calculate risk outcomes (TTS infections, tertiary syphilis in recipients and transfusion-associated congenital syphilis) and cost-effectiveness of alternative testing strategies. The strategies modelled were as follows: universal testing, targeted-testing of high-risk groups (males ≤50 years old and first-time donors) and no testing. RESULTS: The estimated risk of TTS is one in 49·5 million transfusions for universal testing, one in 6 million for targeted-testing of males ≤50 years old, one in 4 million for targeted-testing of first-time donors and one in 2·8 million for no testing. For all strategies, the risk of tertiary and congenital syphilis is <1 in 100 million. Universal testing is the least cost-effective strategy with an incremental cost-effectiveness ratio (ICER) estimated at $538·5 million per disability-adjusted life year averted. CONCLUSION: Universal testing is not required to maintain the risk of TTS within tolerable limits and is estimated to greatly exceed acceptable ICERs for blood safety interventions. However, despite a strong economic and risk-based rationale, given the epidemiology of syphilis in Australia is changing, feedback from critical stakeholders is not currently supportive of reducing testing.

Detection of HFE Haemochromatosis in the clinic and community using standard erythrocyte tests.

Detection of HFE Haemochromatosis (HH) is challenging in the absence of clinical features. HH subjects have elevated erythrocyte parameters compared to those without HH, but it remains unclear how this could be applied in clinical practice. Thus, we determined the sensitivity, specificity and clinical utility of erythrocyte parameters in 144 HH subjects with (n = 122) or without (n = 22) clinical and/or biochemical expression of iron overload, 1844 general population controls, and 700 chronic disease subjects. For both expressing and non-expressing HH subjects, the mean pre- and post-phlebotomy values of mean cell volume (MCV) and mean cell haemoglobin (MCH) were always significantly higher when compared to all other groups and demonstrated excellent diagnostic utility for detection of HH in men and women (AUROC 0.83-0.9; maximal sensitivity and specificity 82% and 78%) using cut-off values for MCV >91 fL or MCH >31 pg, respectively. Between 34 and 62% of all HH subjects would be detected, and <4% of all non-HH subjects would undergo unnecessary testing, if those with MCV or MCH values >94 fL or 32.2 pg, respectively, were evaluated.

The infectious disease blood safety risk of Australian hemochromatosis donations.

BACKGROUND: It has been suggested that blood donors with hereditary hemochromatosis may pose an increased infectious disease risk and adversely affect recipient outcomes. This study compares the infectious disease risk of whole blood (WB) donors enrolled as therapeutic (T) donors to voluntary WB donors to evaluate the safety of blood products provided by the T donors. STUDY DESIGN AND METHODS: This was a retrospective cohort study of all WB donations at the Australian Red Cross Blood Service who donated between January 1, 2011, and December 31, 2013, comparing a yearly mean of 11,789 T donors with 107,773 total donations and a yearly mean of 468,889 voluntary WB donors with 2,584,705 total donations. We compared postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood borne viruses in T and WB donors. RESULTS: Rates of transfusion-transmissible infections in donations destined for component manufacture were significantly lower in therapeutic donations compared to voluntary donations (8.4 vs. 21.6 per 100,000 donations). Bacterial contamination (43.0 vs. 45.9 per 100,000 donations) and postdonation illness reporting (136.2 vs. 110.8 per 100,000 donations) were similar in both cohorts. CONCLUSIONS: The Australian therapeutic venisection program enables T donors to provide a safe and acceptable source of donated WB that has a low infectious disease risk profile.

Evaluating clustering methods within the Artificial Ecosystem Algorithm and their application to bike redistribution in London.

This paper proposes and evaluates a solution to the truck redistribution problem prominent in London's Santander Cycle scheme. Due to the complexity of this NP-hard combinatorial optimisation problem, no efficient optimisation techniques are known to solve the problem exactly. This motivates our use of the heuristic Artificial Ecosystem Algorithm (AEA) to find good solutions in a reasonable amount of time. The AEA is designed to take advantage of highly distributed computer architectures and adapt to changing problems. In the AEA a problem is first decomposed into its relative sub-components; they then evolve solution building blocks that fit together to form a single optimal solution. Three variants of the AEA centred on evaluating clustering methods are presented: the baseline AEA, the community-based AEA which groups stations according to journey flows, and the Adaptive AEA which actively modifies clusters to cater for changes in demand. We applied these AEA variants to the redistribution problem prominent in bike share schemes (BSS). The AEA variants are empirically evaluated using historical data from Santander Cycles to validate the proposed approach and prove its potential effectiveness.

Pain expressiveness and altruistic behavior: an exploration using agent-based modeling.

Predictions which invoke evolutionary mechanisms are hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interactions in specific physical or social environments over many generations. The outcomes have implications for understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/nonexpresser strategies) when injured and of helping, ignoring, or exploiting another in pain (altruistic/nonaltruistic/selfish strategies). Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury interrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, contingencies that evident from experimental work with a variety of mammals, over a few interactions, were replicated in the agent-based model after selection pressure over many generations. More energy-demanding expression of pain reduced its frequency in successive generations, and increasing injury frequency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased expression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits of helping hardly changed its frequency, whereas increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent-based modeling allows simulation of complex behaviors and environmental pressures over evolutionary time.

Therapeutic venesection at the Australian Red Cross Blood Service: impact of the High Ferritin Application on management of hereditary haemochromatosis.

BACKGROUND: Therapeutic venesection is an established treatment for hereditary haemochromatosis. The C282Y homozygotes and C282Y/H63D compound heterozygotes are the most likely human haemochromatosis protein (HFE) variants to cause iron over-load. The principal indications for treatment include iron overload, which is detected through measurement of hepatic iron concentration or a liver biopsy, or suspected iron-overload on the basis of elevated serum ferritin levels. Venesection is not indicated for other HFE genetic variants or in patients with isolated hyperferritinaemia in the absence of the main HFE gene mutations. The Australian Red Cross Blood Service provides a therapeutic venesection program. Since January 2013, referral has been conducted electronically using the novel, web-based High Ferritin Application. OBJECTIVE: The aim of this article is to provide information regarding implementation of the High Ferritin Application and document its im-pact on referral patterns. DISCUSSION: This referral process is based on nationally endorsed, evidence-based algorithms, which have markedly reduced the number of unnecessary therapeutic venesections. An estimated 4000 unnecessary venesections are averted each year and this equates to a saving of $1.4 million.

iStethoscope: a demonstration of the use of mobile devices for auscultation.

iStethoscope Pro is the first piece of software (an "App") produced for iOS devices, which enabled users to exploit their smartphones, music players, or tablets as stethoscopes. The software exploits the built-in microphone (and supports externally added microphones) and performs real-time amplification and filtering to enable heart sounds to be heard with high fidelity. The software also enables the heart sounds to be recorded, analyzed using a spectrogram, and to be transmitted to others via e-mail. This chapter describes the motivation, functionality, and results from this work.

Staging the self-assembly process: inspiration from biological development.

One of the practical challenges facing the creation of self-assembling systems is being able to exploit a limited set of fixed components and their bonding mechanisms. The method of staging divides the self-assembly process into time intervals, during which components can be added to, or removed from, an environment at each interval. Staging addresses the challenge of using components that lack plasticity by encoding the construction of a target structure in the staging algorithm itself and not exclusively in the design of the components. Previous staging strategies do not consider the interplay between component physical features (morphological information). In this work we use morphological information to stage the self-assembly process, during which components can only be added to their environment at each time interval, to demonstrate our concept. Four experiments are presented, which use heterogeneous, passive, mechanical components that are fabricated using 3D printing. Two orbital shaking environments are used to provide energy to the components and to investigate the role of morphological information with component movement in either two or three spatial dimensions. The benefit of our staging strategy is shown by reducing assembly errors and exploiting bonding mechanisms with rotational properties. As well, a doglike target structure is used to demonstrate in theory how component information used at an earlier time interval can be reused at a later time interval, inspired by the use of a body plan in biological development. We propose that a staged body plan is one method toward scaling self-assembling systems with many interacting components. The experiments and body plan example demonstrate, as proof of concept, that staging enables the self-assembly of more complex morphologies not otherwise possible.

The role of chromosome missegregation in cancer development: a theoretical approach using agent-based modelling.

Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reveal a significant difference in the efficacy of different therapy regimes in treating genetically stable and unstable tumours. These data support clinical observations in which a poor prognosis is correlated with a high level of chromosome mis-segregation. However, stochastic simulations run in parallel also exhibit a wide range of behaviours, and the response of individual simulations (equivalent to single tumours) to anti-cancer therapy prove extremely variable. The model therefore highlights the difficulties of predicting the outcome of a given anti-cancer treatment, even in cases in which it is possible to determine the genotype of the entire set of cells within the developing tumour.

Elevated serum ferritin - what should GPs know?

BACKGROUND: Elevated serum ferritin is commonly encountered in general practice. Ninety percent of elevated serum ferritin is due to noniron overload conditions, where venesection therapy is not the treatment of choice. OBJECTIVE: This article aims to outline the role of the Australian Red Cross Blood Service Therapeutic Venesection program, to clarify the interpretation of the HFE gene test and iron studies, and to describe the steps in evaluating a patient with elevated serum ferritin. DISCUSSION: After exclusion of hereditary haemochromatosis, investigation of elevated serum ferritin involves identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors. Referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate if serum ferritin is >1000 µg/L or if the cause of elevated serum ferritin is still unclear.